Patients With P.V142i Transthyretin Mutation: Insights From S Genetic Testing Program

Introduction Heart failure due to cardiomyopathy is a frequent manifestation of hereditary transthyretin amyloidosis (hATTR), a progressive, multisystem, and fatal disease that results from the deposition of misfolded transthyretin (TTR) protein in major organs and systems. Other common symptoms are due to polyneuropathy and carpal tunnel syndrome. The hATTR Compass Program offers confidential genetic testing to patients in the United States, Canada, and Puerto Rico suspected of having hATTR with polyneuropathy or with a family history of hATTR. Hypothesis Patients who have the p.V142I mutation have unique characteristics that are important to recognize. Methods This study analyzed patients with TTR mutations identified by the hATTR Compass Program. DNA samples were analyzed for TTR mutations associated with hATTR amyloidosis using a single-gene test, a polyneuropathy focused 92-gene panel, or a cardiovascular disease focused 81-gene panel. Results Of 165 patients identified with TTR mutations, 130 had the p.V142I mutation; 44.6% were female (n=58/130). The average patient age was 67.5 years (range: 28-87 years). Of patients with confirmed ethnicity, the majority were African American (n=108/130; 83.1%). Overall, 35 patients (26.9%) had a known family history of hATTR, whereas 82 (63.1%) and 13 (10.0%) patients had no family history or did not know, respectively. Many patients had a history of heart disease, cardiac symptoms, or positive cardiac diagnostic tests, as well as symptoms of polyneuropathy. Conclusion Many patients with the p.V142I mutation were identified by genetic testing through the hATTR Compass Program. In this analysis, most patients with p.V142I were African American and commonly presented with a mixed phenotype, including both cardiomyopathy and polyneuropathy. It is critical to recognize symptoms of hATTR amyloidosis and refer patients for genetic testing to facilitate diagnosis of this debilitating, fatal disease.